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Enzyme engineering enables the modification of wild-type proteins to meet industrial and research demands by enhancing catalytic activity, stability, binding affinities, and other properties. The emergence of deep learning methods for protein modeling has demonstrated superior results at lower costs compared to traditional approaches such as directed evolution and rational design. In mutation effect prediction, the key to pre-training deep learning models lies in accurately interpreting the complex relationships among protein sequence, structure, and function. This study introduces a retrieval-enhanced protein language model for comprehensive analysis of native properties from sequence and local structural interactions, as well as evolutionary properties from retrieved homologous sequences. The state-of-the-art performance of the proposed ProtREM is validated on over 2 million mutants across 217 assays from an open benchmark (ProteinGym). We also conducted post-hoc analyses of the model's ability to improve the stability and binding affinity of a VHH antibody. Additionally, we designed 10 new mutants on a DNA polymerase and conducted wet-lab experiments to evaluate their enhanced activity at higher temperatures. Both in silico and experimental evaluations confirmed that our method provides reliable predictions of mutation effects, offering an auxiliary tool for biologists aiming to evolve existing enzymes. The implementation is publicly available at https://github.com/tyang816/ProtREM., Comment: 25 pages, 10 figures, 8 tables

Healthcare industries face challenges when experiencing rare diseases due to limited samples. Artificial Intelligence (AI) communities overcome this situation to create synthetic data which is an ethical and privacy issue in the medical domain. This research introduces the CAT-U-Net framework as a new approach to overcome these limitations, which enhances feature extraction from medical images without the need for large datasets. The proposed framework adds an extra concatenation layer with downsampling parts, thereby improving its ability to learn from limited data while maintaining patient privacy. To validate, the proposed framework's robustness, different medical conditioning datasets were utilized including COVID-19, brain tumors, and wrist fractures. The framework achieved nearly 98% reconstruction accuracy, with a Dice coefficient close to 0.946. The proposed CAT-U-Net has the potential to make a big difference in medical image diagnostics in settings with limited data., Comment: 7 pages, 7 figures

Immunogenicity prediction is a central topic in reverse vaccinology for finding candidate vaccines that can trigger protective immune responses. Existing approaches typically rely on highly compressed features and simple model architectures, leading to limited prediction accuracy and poor generalizability. To address these challenges, we introduce ProVaccine, a novel deep learning solution with a dual attention mechanism that integrates pre-trained latent vector representations of protein sequences and structures. We also compile the most comprehensive immunogenicity dataset to date, encompassing over 9,500 antigen sequences, structures, and immunogenicity labels from bacteria, viruses, and tumors. Extensive experiments demonstrate that ProVaccine outperforms existing methods across a wide range of evaluation metrics. Furthermore, we establish a post-hoc validation protocol to assess the practical significance of deep learning models in tackling vaccine design challenges. Our work provides an effective tool for vaccine design and sets valuable benchmarks for future research., Comment: 18 pages, 11 tables, 5 figures

We explore near-field thermal radiation transport in nanoparticles embedded within a multilayer slab structure, focusing on dynamic modulation of heat flux via cavity interactions. Our findings reveal that by tuning the distance between reflectors and nanoparticles, thermal transport can be significantly suppressed or enhanced, driven by selective excitation of surface modes within the cavity. By precisely adjusting inter-slab gaps, we achieve multi-order control over thermal flux while maintaining stability across a broad range of configurations. Notably, internal slab arrangement plays a pivotal role, with compact designs yielding the most pronounced effects. This work unveils a novel mechanism for manipulating near-field heat transfer, with exciting potential for nanoscale thermal management and thermal sensing technologies.

Enzymes, with their specific catalyzed reactions, are necessary for all aspects of life, enabling diverse biological processes and adaptations. Predicting enzyme functions is essential for understanding biological pathways, guiding drug development, enhancing bioproduct yields, and facilitating evolutionary studies. Addressing the inherent complexities, we introduce a new approach to annotating enzymes based on their catalyzed reactions. This method provides detailed insights into specific reactions and is adaptable to newly discovered reactions, diverging from traditional classifications by protein family or expert-derived reaction classes. We employ machine learning algorithms to analyze enzyme reaction datasets, delivering a much more refined view on the functionality of enzymes. Our evaluation leverages the largest enzyme-reaction dataset to date, derived from the SwissProt and Rhea databases with entries up to January 8, 2024. We frame the enzyme-reaction prediction as a retrieval problem, aiming to rank enzymes by their catalytic ability for specific reactions. With our model, we can recruit proteins for novel reactions and predict reactions in novel proteins, facilitating enzyme discovery and function annotation (https://github.com/WillHua127/ReactZyme).

Accurate prediction of enzyme function is crucial for elucidating biological mechanisms and driving innovation across various sectors. Existing deep learning methods tend to rely solely on either sequence data or structural data and predict the EC number as a whole, neglecting the intrinsic hierarchical structure of EC numbers. To address these limitations, we introduce MAPred, a novel multi-modality and multi-scale model designed to autoregressively predict the EC number of proteins. MAPred integrates both the primary amino acid sequence and the 3D tokens of proteins, employing a dual-pathway approach to capture comprehensive protein characteristics and essential local functional sites. Additionally, MAPred utilizes an autoregressive prediction network to sequentially predict the digits of the EC number, leveraging the hierarchical organization of EC classifications. Evaluations on benchmark datasets, including New-392, Price, and New-815, demonstrate that our method outperforms existing models, marking a significant advance in the reliability and granularity of protein function prediction within bioinformatics.

Charge-order states of broken symmetry, such as charge density wave (CDW), are able to induce exceptional physical properties, however, the precise understanding of the underlying physics is still elusive. Here, we combine fluctuational electrodynamics and density functional theory to reveal an unconventional thermophotonic effect in CDW-bearing TiSe$_2$, referred to as thermophotonic-CDW ($tp$-CDW). The interplay of plasmon polariton and CDW electron excitations give rise to an anomalous negative temperature dependency in thermal photons transport, offering an intuitive fingerprint for a transformation of the electron order. Additionally, the demonstrated nontrivial features of $tp$-CDW transition hold promise for a controllable manipulation of heat flow, which could be extensively utilized in various fields such as thermal science and electron dynamics, as well as in next-generation energy devices., Comment: 7 pages, 4 figures

The Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) has obtained more than 23 million spectra, opening an unprecedented opportunity to study stellar physics, as well as the formation and evolution of our Milky Way. In order to obtain the accurate stellar parameters, we develop a LAMOST Medium-Resolution Spectral Analysis Pipeline (LAMA), which estimates the stellar parameters from the LAMOST medium-resolution spectra, including the effective temperature (Teff), surface gravity (logg), metallicity ([Fe/H]), radial velocity, and rotational velocity (vsini). LAMA estimates these parameters utilizing the template-matching method. The comparison between our results and those from the high-resolution ones, including APOGEE, GALAH, and PASTEL, shows no obvious bias, indicating the reliability of our results. The accuracy of Teff and [Fe/H] can reach 75 K and 0.12 dex, respectively, for the LAMOST Medium-Resolution Spectroscopic Survey (MRS) spectra with a signal-to-noise ratio higher than 10. For dwarfs, the uncertainty of logg is around 0.17 dex, while, for giants, it ranges from 0.18 to 0.30 dex, with the errors decreasing as logg increases. Using LAMA for the LAMOST-MRS spectra, we estimate the stellar parameters of 497,412 stars. This sample will be very helpful for investigating the formation and evolution of our Galaxy., Comment: 18 pages, 21 figures, 4 tables

Highly r-process-enhanced stars are rare and usually metal-poor ([Fe/H] < - 1.0), and mainly populate the Milky Way halo and dwarf galaxies. This study presents the discovery of a relatively bright (V = 12.72), highly r-process-enhanced (r-II) star ([Eu/Fe] = +1.32, [Ba/Eu] = - 0.95), LAMOST J020632.21 + 494127.9. This star was selected from the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) medium-resolution (R ~ 7500) spectroscopic survey; follow-up high-resolution (R ~ 25,000) observations were conducted with the High Optical Resolution Spectrograph (HORuS) installed on the Gran Telescopio Canarias (GTC). The stellar parameters (${T_{\rm eff}}$ = 4130 K, $\rm log\,g $ = 1.52, $ \rm[Fe/H] $ = $ - $0.54, $\xi$ = 1.80 $ \rm{km\,{s^{-1}}} $) have been inferred taking into account non-local thermodynamic equilibrium (NLTE) effects. The abundances of [Ce/Fe], [Pr/Fe], and [Nd/Fe] are +0.19, +0.65 and +0.64, respectively, relatively low compared to the Solar r-process pattern normalized to Eu. This star has a high metallicity ([Fe/H] = - 0.54) compared to most other highly r-process-enhanced stars, and has the highest measured abundance ratio of Eu to H ([Eu/H] = +0.78). It is classified as a thin-disk star based on its kinematics, and does not appear to belong to any known stream or dwarf galaxy., Comment: 5 figures, 3 tables

The advent of deep learning has introduced efficient approaches for de novo protein sequence design, significantly improving success rates and reducing development costs compared to computational or experimental methods. However, existing methods face challenges in generating proteins with diverse lengths and shapes while maintaining key structural features. To address these challenges, we introduce CPDiffusion-SS, a latent graph diffusion model that generates protein sequences based on coarse-grained secondary structural information. CPDiffusion-SS offers greater flexibility in producing a variety of novel amino acid sequences while preserving overall structural constraints, thus enhancing the reliability and diversity of generated proteins. Experimental analyses demonstrate the significant superiority of the proposed method in producing diverse and novel sequences, with CPDiffusion-SS surpassing popular baseline methods on open benchmarks across various quantitative measurements. Furthermore, we provide a series of case studies to highlight the biological significance of the generation performance by the proposed method. The source code is publicly available at https://github.com/riacd/CPDiffusion-SS, Comment: 10 pages, 4 figures

Deep learning has become a crucial tool in studying proteins. While the significance of modeling protein structure has been discussed extensively in the literature, amino acid types are typically included in the input as a default operation for many inference tasks. This study demonstrates with structure alignment task that embedding amino acid types in some cases may not help a deep learning model learn better representation. To this end, we propose ProtLOCA, a local geometry alignment method based solely on amino acid structure representation. The effectiveness of ProtLOCA is examined by a global structure-matching task on protein pairs with an independent test dataset based on CATH labels. Our method outperforms existing sequence- and structure-based representation learning methods by more quickly and accurately matching structurally consistent protein domains. Furthermore, in local structure pairing tasks, ProtLOCA for the first time provides a valid solution to highlight common local structures among proteins with different overall structures but the same function. This suggests a new possibility for using deep learning methods to analyze protein structure to infer function., Comment: 8 pages, 4 figures

Understanding protein solubility is essential for their functional applications. Computational methods for predicting protein solubility are crucial for reducing experimental costs and enhancing the efficiency and success rates of protein engineering. Existing methods either construct a supervised learning scheme on small-scale datasets with manually processed physicochemical properties, or blindly apply pre-trained protein language models to extract amino acid interaction information. The scale and quality of available training datasets leave significant room for improvement in terms of accuracy and generalization. To address these research gaps, we propose \sol, a novel deep learning method that combines pre-training and fine-tuning schemes for protein solubility prediction. ProtSolM integrates information from multiple dimensions, including physicochemical properties, amino acid sequences, and protein backbone structures. Our model is trained using \data, the largest solubility dataset that we have constructed. PDBSol includes over $60,000$ protein sequences and structures. We provide a comprehensive leaderboard of existing statistical learning and deep learning methods on independent datasets with computational and experimental labels. ProtSolM achieved state-of-the-art performance across various evaluation metrics, demonstrating its potential to significantly advance the accuracy of protein solubility prediction., Comment: 10 pages, 7 figures, 9 tables

We explore a novel approach to achieving anisotropic thermal photon tunneling, inspired by the concept of parity-time symmetry in quantum physics. Our method leverages the modulation of constitutive optical parameters, oscillating between loss and gain regimes. This modulation reveals a variety of distinct effects in thermal photon behavior and dispersion. Specifically, we identify complex tunneling modes through gain-loss engineering, which include thermal photonic defect states and Fermi-arc-like phenomena, which surpass those achievable through traditional polariton engineering. Our research also elucidates the laws governing the evolution of radiative energy in the presence of gain and loss interactions, and highlights the unexpected inefficacy of gain in enhancing thermal photon energy transport compared to systems characterized solely by loss. This study not only broadens our understanding of thermal photon tunneling but also establishes a versatile platform for manipulating photon energy transport, with potential applications in thermal management, heat science, and the development of advanced energy devices., Comment: 8 pages, 5 figures

High-accuracy microwave sensing is widely demanded in various fields, ranging from cosmology to microwave quantum technology. Quantum receivers based on inorganic solid-state spin systems are promising candidates for such purpose because of the stability and compatibility, but their best sensitivity is currently limited to a few pT/$\sqrt{\rm{Hz}}$. Here, by utilising an enhanced readout scheme with the state-of-the-art solid-state maser technology, we develop a robust microwave quantum receiver functioned by organic molecular spins at ambient conditions. Owing to the maser amplification, the sensitivity of the receiver achieves 6.14 $\pm$ 0.17 fT/$\sqrt{\rm{Hz}}$ which exceeds three orders of magnitude than that of the inorganic solid-state quantum receivers. The heterodyne detection without additional local oscillators improves bandwidth of the receiver and allows frequency detection. The scheme can be extended to other solid-state spin systems without complicated control pulses and thus enables practical applications such as electron spin resonance spectroscopy, dark matter searches, and astronomical observations., Comment: 10 pages, 4 figures

The expanding role of Artificial Intelligence (AI) in diverse engineering domains highlights the challenges associated with deploying AI models in new operational environments, involving substantial investments in data collection and model training. Rapid application of AI necessitates evaluating the feasibility of utilizing pre-trained models in unobserved operational settings with minimal or no additional data. However, interpreting the opaque nature of AI's black-box models remains a persistent challenge. Addressing this issue, this paper proposes a science-based certification methodology to assess the viability of employing pre-trained data-driven models in new operational environments. The methodology advocates a profound integration of domain knowledge, leveraging theoretical and analytical models from physics and related disciplines, with data-driven AI models. This novel approach introduces tools to facilitate the development of secure engineering systems, providing decision-makers with confidence in the trustworthiness and safety of AI-based models across diverse environments characterized by limited training data and dynamic, uncertain conditions. The paper demonstrates the efficacy of this methodology in real-world safety-critical scenarios, particularly in the context of traffic state estimation. Through simulation results, the study illustrates how the proposed methodology efficiently quantifies physical inconsistencies exhibited by pre-trained AI models. By utilizing analytical models, the methodology offers a means to gauge the applicability of pre-trained AI models in new operational environments. This research contributes to advancing the understanding and deployment of AI models, offering a robust certification framework that enhances confidence in their reliability and safety across a spectrum of operational conditions., Comment: 7 Pages, 5 figures, \c{opyright}2024 IEEE INTERNATIONAL CONFERENCE on ELECTRO/INFORMATION TECHNOLOGY

This paper investigates the stochastic behavior of an n-node blockchain which is continuously monitored and faces non-stop cyber attacks from multiple hackers. The blockchain will start being re-set once hacking is detected, forfeiting previous efforts of all hackers. It is assumed the re-setting process takes a random amount of time. Multiple independent hackers will keep attempting to hack into the blockchain until one of them succeeds. For arbitrary distributions of the hacking times, detecting times, and re-setting times, we derive the instantaneous functional probability, the limiting functional probability, and the mean functional time of the blockchain. Moreover, we establish that these quantities are increasing functions of the number of nodes, formalizing the intuition that the more nodes a blockchain has the more secure it is.

Fine-tuning Pre-trained protein language models (PLMs) has emerged as a prominent strategy for enhancing downstream prediction tasks, often outperforming traditional supervised learning approaches. As a widely applied powerful technique in natural language processing, employing Parameter-Efficient Fine-Tuning techniques could potentially enhance the performance of PLMs. However, the direct transfer to life science tasks is non-trivial due to the different training strategies and data forms. To address this gap, we introduce SES-Adapter, a simple, efficient, and scalable adapter method for enhancing the representation learning of PLMs. SES-Adapter incorporates PLM embeddings with structural sequence embeddings to create structure-aware representations. We show that the proposed method is compatible with different PLM architectures and across diverse tasks. Extensive evaluations are conducted on 2 types of folding structures with notable quality differences, 9 state-of-the-art baselines, and 9 benchmark datasets across distinct downstream tasks. Results show that compared to vanilla PLMs, SES-Adapter improves downstream task performance by a maximum of 11% and an average of 3%, with significantly accelerated training speed by a maximum of 1034% and an average of 362%, the convergence rate is also improved by approximately 2 times. Moreover, positive optimization is observed even with low-quality predicted structures. The source code for SES-Adapter is available at https://github.com/tyang816/SES-Adapter., Comment: 30 pages, 4 figures, 8 tables

Accurately characterizing intrinsic stellar photometric noise induced by stellar astrophysics, such as stellar activity, granulation, and oscillations, is of crucial importance for detecting transiting exoplanets. In this study, we investigate the relation between the intrinsic stellar photometric noise, as quantified by the Kepler rrmsCDPP measurement, and the level of stellar chromospheric activity, as indicated by the S-index of Ca II HK lines derived from the LAMOST spectra. Our results reveal a clear positive correlation between S-index and rrmsCDPP, and the correlation becomes more significant at higher activity levels and on longer timescales. We have therefore built an empirical relation between rrmsCDPP and S-index as well as Teff, logg, [Fe/H], and apparent magnitude with the XGBoost regression algorithm, using the LAMOST-Kepler common star sample as the training set. This method achieves a precision of ~20 ppm for inferring the intrinsic noise from the S-index and other stellar labels on a 6-hour integration duration. We have applied this empirical relation to the full LAMOST DR7 spectra database, and obtained the intrinsic noise predictions for 1,358,275 stars. The resultant catalog is publicly available and expected to be valuable for optimizing target selection for future exoplanet-hunting space missions, such as the Earth 2.0 mission., Comment: Accepted for publication in ApJS

RNA design shows growing applications in synthetic biology and therapeutics, driven by the crucial role of RNA in various biological processes. A fundamental challenge is to find functional RNA sequences that satisfy given structural constraints, known as the inverse folding problem. Computational approaches have emerged to address this problem based on secondary structures. However, designing RNA sequences directly from 3D structures is still challenging, due to the scarcity of data, the non-unique structure-sequence mapping, and the flexibility of RNA conformation. In this study, we propose RiboDiffusion, a generative diffusion model for RNA inverse folding that can learn the conditional distribution of RNA sequences given 3D backbone structures. Our model consists of a graph neural network-based structure module and a Transformer-based sequence module, which iteratively transforms random sequences into desired sequences. By tuning the sampling weight, our model allows for a trade-off between sequence recovery and diversity to explore more candidates. We split test sets based on RNA clustering with different cut-offs for sequence or structure similarity. Our model outperforms baselines in sequence recovery, with an average relative improvement of $11\%$ for sequence similarity splits and $16\%$ for structure similarity splits. Moreover, RiboDiffusion performs consistently well across various RNA length categories and RNA types. We also apply in-silico folding to validate whether the generated sequences can fold into the given 3D RNA backbones. Our method could be a powerful tool for RNA design that explores the vast sequence space and finds novel solutions to 3D structural constraints., Comment: 15 pages

The expanding role of Artificial Intelligence (AI) in diverse engineering domains highlights the challenges associated with deploying AI models in new operational environments, involving substantial investments in data collection and model training. Rapid application of AI necessitates evaluating the feasibility of utilizing pre-trained models in unobserved operational settings with minimal or no additional data. However, interpreting the opaque nature of AI's black-box models remains a persistent challenge. Addressing this issue, this paper proposes a science-based certification methodology to assess the viability of employing pre-trained data-driven models in untrained operational environments. The methodology advocates a profound integration of domain knowledge, leveraging theoretical and analytical models from physics and related disciplines, with data-driven AI models. This novel approach introduces tools to facilitate the development of secure engineering systems, providing decision-makers with confidence in the trustworthiness and safety of AI-based models across diverse environments characterized by limited training data and dynamic, uncertain conditions. The paper demonstrates the efficacy of this methodology in real-world safety-critical scenarios, particularly in the context of traffic state estimation. Through simulation results, the study illustrates how the proposed methodology efficiently quantifies physical inconsistencies exhibited by pre-trained AI models. By utilizing analytical models, the methodology offers a means to gauge the applicability of pre-trained AI models in new operational environments. This research contributes to advancing the understanding and deployment of AI models, offering a robust certification framework that enhances confidence in their reliability and safety across a spectrum of operational conditions., Comment: 7 pages, 4 figures

In the healthcare domain, Magnetic Resonance Imaging (MRI) assumes a pivotal role, as it employs Artificial Intelligence (AI) and Machine Learning (ML) methodologies to extract invaluable insights from imaging data. Nonetheless, the imperative need for patient privacy poses significant challenges when collecting data from diverse healthcare sources. Consequently, the Deep Learning (DL) communities occasionally face difficulties detecting rare features. In this research endeavor, we introduce the Ensemble-Based Federated Learning (EBFL) Framework, an innovative solution tailored to address this challenge. The EBFL framework deviates from the conventional approach by emphasizing model features over sharing sensitive patient data. This unique methodology fosters a collaborative and privacy-conscious environment for healthcare institutions, empowering them to harness the capabilities of a centralized server for model refinement while upholding the utmost data privacy standards.Conversely, a robust ensemble architecture boasts potent feature extraction capabilities, distinguishing itself from a single DL model. This quality makes it remarkably dependable for MRI analysis. By harnessing our groundbreaking EBFL methodology, we have achieved remarkable precision in the classification of brain tumors, including glioma, meningioma, pituitary, and non-tumor instances, attaining a precision rate of 94% for the Global model and an impressive 96% for the Ensemble model. Our models underwent rigorous evaluation using conventional performance metrics such as Accuracy, Precision, Recall, and F1 Score. Integrating DL within the Federated Learning (FL) framework has yielded a methodology that offers precise and dependable diagnostics for detecting brain tumors., Comment: 6

Semantic segmentation of high-resolution remote sensing imagery (HRSI) suffers from the domain shift, resulting in poor performance of the model in another unseen domain. Unsupervised domain adaptive (UDA) semantic segmentation aims to adapt the semantic segmentation model trained on the labeled source domain to an unlabeled target domain. However, the existing UDA semantic segmentation models tend to align pixels or features based on statistical information related to labels in source and target domain data, and make predictions accordingly, which leads to uncertainty and fragility of prediction results. In this paper, we propose a causal prototype-inspired contrast adaptation (CPCA) method to explore the invariant causal mechanisms between different HRSIs domains and their semantic labels. It firstly disentangles causal features and bias features from the source and target domain images through a causal feature disentanglement module. Then, a causal prototypical contrast module is used to learn domain invariant causal features. To further de-correlate causal and bias features, a causal intervention module is introduced to intervene on the bias features to generate counterfactual unbiased samples. By forcing the causal features to meet the principles of separability, invariance and intervention, CPCA can simulate the causal factors of source and target domains, and make decisions on the target domain based on the causal features, which can observe improved generalization ability. Extensive experiments under three cross-domain tasks indicate that CPCA is remarkably superior to the state-of-the-art methods., Comment: 16 pages, 8 figures and 7 tables, submitted to IEEE Transactions on Geoscience and Remote Sensing, 2024

Lithium is a fragile but crucial chemical element in the universe, exhibits interesting and complex behaviors. Thanks to the massive spectroscopic data from the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) medium-resolution survey (MRS), we can investigate the lithium abundances in a large and diverse sample of stars, which could bring vital help to study the origin and evolution of lithium. In this work, we use the Li 6,707.8 {\AA} line to derive the lithium abundance through a template-matching method. A catalog of precise lithium abundance is presented for 795,384 spectra corresponding to 455,752 stars from the LAMOST MRS Data Release (DR) 9. Comparing our results with those of external high-resolution references we find a good consistency with a typical deviation of {\sigma} A(Li) ~ 0.2 dex. We also analyze the internal errors using stars that have multiple LAMOST MRS observations, which will reach as low as 0.1 dex when the signal-to-noise ratio (S/N) of the spectra > 20. Besides, our result indicates that a small fraction of giant stars still exhibit surprisingly high amount of lithium contents, and 967 stars are identified as Li-rich giants with A(Li) > 1.5 dex, accounting for ~ 2.6% of our samples. If one takes into account the fact that nearly all stars deplete lithium during the main sequence, then the fraction of Li-rich stars may exceed 2.6% much. This new catalog covers a wide range of stellar evolutionary stages from pre-main sequence to giants, and will provide help to the further study of the chemical evolution of lithium., Comment: 16 pages, 9 figures, 2 tables. Accepted for publication in ApJS

The emerging trend of advancing generalist artificial intelligence, such as GPTv4 and Gemini, has reshaped the landscape of research (academia and industry) in machine learning and many other research areas. However, domain-specific applications of such foundation models (e.g., in medicine) remain untouched or often at their very early stages. It will require an individual set of transfer learning and model adaptation techniques by further expanding and injecting these models with domain knowledge and data. The development of such technologies could be largely accelerated if the bundle of data, algorithms, and pre-trained foundation models were gathered together and open-sourced in an organized manner. In this work, we present OpenMEDLab, an open-source platform for multi-modality foundation models. It encapsulates not only solutions of pioneering attempts in prompting and fine-tuning large language and vision models for frontline clinical and bioinformatic applications but also building domain-specific foundation models with large-scale multi-modal medical data. Importantly, it opens access to a group of pre-trained foundation models for various medical image modalities, clinical text, protein engineering, etc. Inspiring and competitive results are also demonstrated for each collected approach and model in a variety of benchmarks for downstream tasks. We welcome researchers in the field of medical artificial intelligence to continuously contribute cutting-edge methods and models to OpenMEDLab, which can be accessed via https://github.com/openmedlab., Comment: Technical Report. Visit https://github.com/openmedlab for more details

Accurately modeling the protein fitness landscapes holds great importance for protein engineering. Recently, due to their capacity and representation ability, pre-trained protein language models have achieved state-of-the-art performance in predicting protein fitness without experimental data. However, their predictions are limited in accuracy as well as interpretability. Furthermore, such deep learning models require abundant labeled training examples for performance improvements, posing a practical barrier. In this work, we introduce FSFP, a training strategy that can effectively optimize protein language models under extreme data scarcity. By combining the techniques of meta-transfer learning, learning to rank, and parameter-efficient fine-tuning, FSFP can significantly boost the performance of various protein language models using merely tens of labeled single-site mutants from the target protein. The experiments across 87 deep mutational scanning datasets underscore its superiority over both unsupervised and supervised approaches, revealing its potential in facilitating AI-guided protein design.

The gold standard for designing a search plan is to select a target distribution and then find the uniformly optimal search plan based on it. This approach has been successfully applied in several high-profile civil and military search missions. Since the target distribution is subjective and chosen at an analyst's discretion, it is natural to ask whether this approach can generate a search plan that maximizes the true detection probability at each moment. This article gives a negative answer by establishing that, under mild conditions, for a given target distribution and the optimal search plan based on it, there is another target distribution whose induced uniformly optimal search plan leads to an increased true detection probability at every moment. In particular, it implies that the problem of finding a search plan that maximizes the true detection probability at each moment remains unsolved.

Third-party intellectual property cores are essential building blocks of modern system-on-chip and integrated circuit designs. However, these design components usually come from vendors of different trust levels and may contain undocumented design functionality. Distinguishing such stealthy lightweight malicious design modification can be a challenging task due to the lack of a golden reference. In this work, we make a step towards design for assurance by developing a method for identifying and preventing hardware Trojans, employing functional verification tools and languages familiar to hardware designers. We dump synthesized design netlist mapped to a field programmable gate array technology library and perform switching as well as coverage analysis at the granularity of look-up-tables (LUTs) in order to identify specious signals and cells. We automatically extract and formally prove properties related to switching and coverage, which allows us to retrieve Trojan trigger condition. We further provide a solution to preventing Trojan from activation by reconfiguring the confirmed malicious LUTs. Experimental results have demonstrated that our method can detect and mitigate Trust-Hub as well as recently reported don't care Trojans.

Large protein language models are adept at capturing the underlying evolutionary information in primary structures, offering significant practical value for protein engineering. Compared to natural language models, protein amino acid sequences have a smaller data volume and a limited combinatorial space. Choosing an appropriate vocabulary size to optimize the pre-trained model is a pivotal issue. Moreover, despite the wealth of benchmarks and studies in the natural language community, there remains a lack of a comprehensive benchmark for systematically evaluating protein language model quality. Given these challenges, PETA trained language models with 14 different vocabulary sizes under three tokenization methods. It conducted thousands of tests on 33 diverse downstream datasets to assess the models' transfer learning capabilities, incorporating two classification heads and three random seeds to mitigate potential biases. Extensive experiments indicate that vocabulary sizes between 50 and 200 optimize the model, whereas sizes exceeding 800 detrimentally affect the model's representational performance. Our code, model weights and datasets are available at https://github.com/ginnm/ProteinPretraining., Comment: 46 pages, 4figures, 9 tables

The number of active shooter incidents in the US has been increasing alarmingly. It is imperative for the government as well as the public to understand these events. Though both analytic and agent-based models have been proposed for studying active shooter incidents, there are only a few analytic models in the literature, and none incorporates civilian resistance. This article analytically investigates the optimal action of a civilian during an active shooter incident when he can hide, fight, or run.